Effect of Urine Alkalinazation on Urinary Inflammatory Markers in Patients With Cystinuria

European Georges Pompidou Hospital63 enrolled

Overview

It has recently been described the presence of a urinary inflammatory signature in patients with cystinuria, the most common cause of renal lithiasis of genetical origin. These data are very innovative in this pathology but deserve further studies to establish the specificity of this inflammatory signature in patients with cystinuria compared to other nephropathies and other renal lithiasis diseases. Moreover, the effect of the usual treatment of cystinuria (namely urine alkalanization) on urinary inflammatory biomarkers deserves to be tested. The objectives of the present study are: i) To study the urinary inflammatory profile by mass spectrometry (a very efficient tool to detect and identify proteins) in patients with cystinuria and in patients with lithiasis of other origin and in patients with inflammatory renal disease ; ii) To study the potential effect of urine alkalinazation with potassium citrate (usual treatment according to European recommendations) on the inflammatory signature of patients with cystinuria. To this aim, urine of non treated cystinuric patients will be collected before treatement initiation and 3 months after the start of the alkalizing treatment.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Cystinuria Renal Lithiasis Glomerulonephritis Interstitial Nephritis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * age superior or equal to 18 years * patient able to understand the information note and to sign the informed consent * patient with an Health coverage * no current urinary tract infection (assessed by a cytobacteriological examination of the urine) * For the cystinuria group: patient with cystinuria not yet treated or for whom the alkalizing treatment or the cystein binding thiol agents have been discontinuated for at least 3 months AND with an estimated GFR (using the MDRD formula) greater than 60 ml/min/1.73m2. * For the control groups: patient presenting either a renal lithiasis not due to cystinuria, or an inflammatory renal pathology confirmed by an anterior renal biopsy (glomerulonephritis or interstitial nephritis) AND with an estimated GFR (using the MDRD formula) greater than 30 ml/ min/1.73m2. Exclusion Criteria: * Cystinuric patient already treated (whatever the treatment)

Outcomes

Primary Outcomes

Change from baseline urine inflammatory profile after 3 months of alkalizing treatment using mass spectrometry in patients with cystinuria.

Study of urine inflammatory biomarkers profile using mass spectrometry to determine if the alkalizing treatment is susceptible to modify the urine inflammatory profile. Proteases inhibitors will be added to the urine sample immediately after urination. Urine will then be frozen at -80°C until mass spectrometry analysis. Mass spectrometry will determine the differential expression of all the proteins present the urine sample. For the purpose of the present study, the investigators will focus on the expression of inflammatory biomarkers among them MMP9 (matrix metallopeptidase), Myeloperoxydase, Proteinase 3, Neutrophil Elastase, Cathepsine G, LSP1 (lymphocyte specific protein), Fibrinogen beta and gamma chains. The aim of mass spectrometry is to detect the presence of proteins in the urine sample and to assess the differential levels of expression of the detected proteins but not to precisely measure the urine concentration of the detected proteins.

Time frame: at inclusion and after three months of the usual alkalizing treatment for the patients with cystinuria

Secondary Outcomes

Assessment of urine inflammatory profile in controls groups using mass spectrometry.

Study of urine inflammatory biomarkers with mass spectrometry in control groups to determine if the urine inflammatory profile is specific to cystinuria. Proteases inhibitors will be added to the urine sample immediately after urination. Urine will then be frozen at -80°C until analysis. Mass spectrometry will determine the differential expression of all the proteins present the urine sample. For the purpose of the present study, the investigators will focus on the expression of inflammatory biomarkers. The aim of mass spectrometry is to detect the presence of proteins in the urine sample and to assess the differential levels of expression of the detected proteins but not to precisely measure the urine concentration of these proteins. Moreover, urine analysis by mass spectrometry will detect all urinary proteins and the investgators do exclude to find unexpected proteins. For those reasons, urine analysis by mass spectrometry is a unique outcome.

Time frame: at inclusion for patients with a nephrolithiasis not due to cystinuria and in patients an inflammatory nephropathy of glomerular or tubulo interstitial origin

Study of crystalluria (presence of crystals in urine) to assess nephrolithiasis activity.

Assessment of the presence of crystals in the second morning urine sample in patients with cystinuria and in patients with a nephrolithiasis not due to cystinuria, to assess nephrolithiasis activity.

Time frame: at inclusion for these two groups and after three months of the usual alkalizing treatment for the patients with cystinuria